David Horrobin and Schizophrenia

MAD-bookDavid Horrobin MD, PhD, was one of the leading fatty acid researchers in the world. He had a life-time fascination with schizophrenia which culminated in his 2001 publication, “The Madness of Adam and Eve”. He believed that schizophrenia is a leading characteristic of mankind that makes us human. Not the debilitating versions of the disorder, but milder significant variations that contributed to a higher level of achievement in the realms of politics, religion, science, and the arts. The history of prominent world leaders who were schizophrenic or had a prevalence of the disorder in their families ranged from Da Vinci, Newton, Van Gogh, Einstein, even Churchill. What Horrobin firmly believes is that schizophrenia lies at the very foundation of human culture.

MAD-DavidHHorrobin was a brilliant Oxford student earning him two scholarships to Balliol resulting in a doctorate in neuroscience. He later became a Fellow of Magdalen College where he studied medicine. Shortly thereafter he received a prize fellowship to a chair in physiology at the Nairobi Medical School in Kenya and later a Professorship of Medicine at the University of Montreal. Unfortunately, we lost him to cancer in April 2003. He was only 64 but during his lifetime authored or participated in 939 publications, receiving a further 114 patents in which he is a named inventor, bringing the grand total to 1053. From his first publication in 1964 to his death, this equates to one publication every two weeks for 39 years – a prodigious achievement. He also developed fatty acid supplements that were revolutionary for their time, one of which was Kirunal which he formulated specifically for schizophrenia, and to a lesser degree, bipolar, which he describes in chapter 17 of “The Madness”. The book is currently out of print, however, used copies and an imported paperback are available on Amazon.

Dr. Horrobin describes his collaboration with Malcolm Peet and Krishna Vaddadi and others who worked with chronic, difficult to-treat schizophrenic patients. Vaddadi’s early work in the field found that fatty acid abnormalities, specifically low arachidonic acid (AA), when exposed to a fever, manifested an improved mental and physical states. Schizophrenics also demonstrate resistance to pain and arthritis which is indicative of low AA (Horrobin 1995, 1998). These symptoms were corroborated in the patients’ red blood cell fatty acid test scores which showed a deficiency in both omega 6 (AA) and omega 3 (DHA) (Peet 2008).

Vaddadi, a Professor of Psychiatry at Monash University in Melbourne, was first to use gamma-linolenic acid (GLA, an AA precursor) to modulate schizotypal symptoms. However, the results were modest and too insignificant to rely on as a treatment (Vaddadi 1989, 2006). About the same time Horrobin and Peet collected additional evidence that omega-3’s as well as omega-6 fatty acids were deficient in schizophrenic patients (Horrobin 1994, Peet 1995). Shortly thereafter they began a series of trials that included both EPA and DHA from fish oils, focusing first on a higher concentration of one and then the other. They were shocked to learn that higher DHA levels did not improve the symptoms, in fact, the outcome was slightly negative. It was EPA that was beneficial; hence the focus on Kirunal which is formulated with twice the EPA to DHA ratio at 3 to 1 instead of the standard fish oil ratio of 1-1/2 to 1.

Case Study

Jonathon was thirty-one years old and had had a schizophrenic breakdown at the age of nineteen which caused him to drop out of college. Earlier he had received a single dose of an anti-schizophrenic drug but experienced such a severe adverse reaction that he vowed “never again – no drugs for me”. For ten years he drifted around London, leading the all-too-typical life of an unemployed schizophrenic patient. Peet was approached by Jonathon’s doctors who wanted to try Kirunal. Jonathan took 8gr a day providing him with about 2gr a day of pure EPA.

After four weeks there was no effect on his psychiatric state. His delusions, his auditory hallucinations and his general apathy were unchanged. But Alex, Jonathon’s doctor, felt that there was some improvement but difficult to define. She felt that he looked healthier, and that his skin and hair condition had improved. By eight weeks, Jonathan and Alex realized that something important had happened. Jonathan was clearly better. His appearance was transformed. He was more alert; more interested in life and had experienced a dramatic reduction in his delusions and hallucinations.

MAD-cellmembraneOne of the reasons why Alex was so interested in Jonathan was that he was dyslexic as well. She noted that on her tests for dyslexia his performance was improving. It was now quite easy to persuade Jonathan to continue with Kirunal. Over the following twelve months Jonathan progressively improved with regard to all aspects of his condition. After twelve years of illness, his scores on the schizophrenia rating scales were somewhat above the normal mean but not by much. People meeting him for the first time thought him somewhat quirky and unusual but certainly not schizophrenic. His dyslexia also improved substantially and he began to contemplate the idea of going back to school. Now, three years after starting the higher EPA fish oil, he has returned to college. But perhaps the most exciting aspect of Jonathan’s Kirunal treatment from the point of view of Alex is that his brain changes, as seen on the MRI scans, had reversed. He regained some of the brain tissue, the loss of which everyone believed to be permanent.

Meanwhile Malcolm Peet and Ramchand, a scientist from India, working together at Sheffield together with The Schizophrenia Association of Great Britain, organized a larger trial using Kirunal with 63 patients in Wales. The results matched Jonathon’s exciting success, but, in various degrees. For more complete details pick up a copy of the “The Madness”.

BodyBio: BodyBio was drawn into the schizophrenic scene from their research and extensive studies into psychosis and neurologic disorders and especially after the purchase of the Kirunal product line from the estate of David Horrobin after his death. Although BodyBio is a manufacturer of nutrients, it is predominantly a scientifically based research company focusing on the nutritional aspects of Fatty Acids (FA) such as Kirunal and conducts a series of lectures to doctors’ on the subject worldwide. After years of medical counseling and tracking patient’s results, BodyBio has realized that there is no single drug or nutritional answers for healing. As Vaddadi and Peet have shown prior, deficiencies in fatty acids can be confirmed by a red cell fatty acid analysis, which BodyBio has been performing for doctors for ~15 years. The lab work is performed at Johns Hopkins that is the gold standard fatty acid laboratory in the world. Fatty acids are a complex subject which BodyBio attempts to unravel for physicians and health care professionals through a proprietary computerized analysis to help clinicians digest the complex results for their patients.

FO-KirunalBasically, Kirunal is not a drug, it’s a food supplement. It is an omega 3 combination of fish oil constituents. It should be administered with respect to the body’s need for dietary balance between the n-3 FAs (EPA and DHA) and the n-6 FAs (AA). There are ~100 billion neurons in our brains which have a high concentration of arachidonic acid (AA) and docosahexaenoic acid (DHA). Horrobin says that the dry weight of the brain is 60% FAs and the DHA and AA content is 20% of that total (“The Madness”).

article1-PC-moleculeWhile these constitute 80-90% of the essential polyunsaturated fatty acids in our neuronal tissues, there is a deficit of AA in schizophrenia (Kim 2010), which is best obtained from diet (eggs, dairy, meat, fish and shellfish). Glen in ’94, reported that while there is a disturbed fatty acid profile in both negative and positive schizophrenics, the different forms take an opposite FA pathway. Those with negative symptoms are high in saturated FAs and low in the poly-unsaturates, while the reverse occurs in those with positive symptoms. However, all schizophrenics are low in both AA and DHA which is caused by an over-expression of phospholipaseA2 (PLA2). PLA2 is a lipase which cleaves off the FA on the sn2 position (the middle of the phospholipid molecule) where AA and DHA normally reside. This is a normal function, which, in schizophrenics is over-expressed, and which prematurely frees up much of the bound AA and DHA, dumping them into the FA pool, and effectively wasting the two most vital FAs in the brain. EPA (high in Kirunal) has the ability to lower PLA2, which in effect, would tend to keep AA in the membrane ready and waiting to become the all-important eicosanoid/prostaglandin, and, at the same time, keeping DHA there as well where it can perform its high-wire act facilitating neurotransmitter release.

When treating schizophrenia, psychiatrists are accustomed to the idea that it is better to use a single drug rather than poly-pharmacy. The same approach is taken when investigating any new treatments. However, nutritional treatments are different. Nutrients are normally ingested in complex combinations with food, and in normal physiology they act synergistically. Either deficiency or excess of a particular nutrient can have harmful effects. In schizophrenia, there is evidence for benefits, not only from omega-3 PUFAs, which would include DHA, and the n-6 PUFA for AA, but also from other nutrients. These include the “homocysteine-lowering” vitamins folate, B6, and B12 (Levine 2006), and the antioxidant vitamins (Peet 2008).

MAD-tree-renderingEarlier, in private discussions between Dr. Horrobin and Patricia Kane, PhD, (BodyBio’s Chief Medical Advisor), he confirmed the importance of fatty acid balance, and specifically noted that with Jonathon, as well as with all studies involving Kirunal, patients were encouraged to add into their diet foods high in omega 6 PUFAs like AA, high in eggs, butter and cream. He also made a special effort to lower sugar intake; however, that was not always successful.

Of special interest in the two journals both authored by Peet, Glen, and Horrobin on Schizophrenia and the Biochemistry of Phospholipids, “Phospholipid Spectrum Disorder in Psychiatry, 1999” and 2003”, there is extensive discussion on phospholipid metabolism. However, both journals predominantly lean towards genetics and the consumate protein and peptide functions in signal transduction. There is, however, a total absence of the clinical use of phospholipids, specifically phosphatidylcholine (PC), which has had a long history of success in clinics worldwide for over 30 years as either an IV infusion or an oral supplement. Brian Ross reporting in chapter two of the first edition, “Numerous, though not all, investigators have observed that levels of the major membrane phospholipids, phosphatidylcholine and phosphatidylethanolamine, are decreased in erythrocytes, platelets, and skin fibroplasts of patients with schizophrenia.” However, the observation from Ross never made its way into Horrobin’s scientific exploration with psychosis and schizophrenia. This is the exact arena where BodyBio has had much success bringing both PC and PE directly into the clinic as either an IV or orally, and more importantly, introducing it directly to the doctors and their patients with psychosis. Unfortunately, David’s life struggle occurred about the same time that Dr. Kane was beginning her clinical success with PC.

There are two more important parts to the fatty acid / schizophrenic equation, which exists in a large part with all neurological disturbances and all metabolism as well, that is (1) the need for a more correct dietary intake of the base essential oils, n-6 Linoleic Acid, and n-3 Alpha Linolenic acid (Yehuda et al. 1993-2008), and (2) the loss of phospholipids as mentioned above by Ross, predominantly phosphatidylcholine (PC), as we age or become ill (Yechiel 1985, Hennis 1085). BodyBio has a long history of teaching clinicians on the science of balancing FAs (6s and 3s) and the use of both oral and i.v. administration of PC.

An interesting sequel in the effort of finding an answer for the “schizophrenia problem” is the clinical use of phospholipids, specifically phosphatidylcholine (PC). PC as Essentiale and Lipostabil has been available in Europe since the ‘70s. Both were 5 ml i.v. ampoules of PC used to rebuild the membrane phospholipids (think improved signal transmission). Essentiale (Aventis) focused on liver disease and Lipostabil (Rhone Poulanc) primarily addressed cardiovascular disorders. Both have a long history of success, especially in the former Eastern bloc countries where every doctor in that large part of the world used i.v. PC therapy to rehabilitate Russian livers from the over consumption of vodka, which either Essentiale or Lipostabil can effectively do, and which, as you might imagine, is a recurring event. We can only assume that Horrobin and his group of competent researchers who followed his lead were aware of some of the medical history of the medical use of PC.

The sequel really started with Dr. Patricia Kane of BodyBio who had researched those early years of success with IV PC and thought “why not apply it for neurological disorders”, which has since performed equally well for all the neurological disorders of our day, Parkinson’s, Alzheimer’s, MS, fibromyalgia, Autism, erythromelogia, etc. However, that was just about the time we lost David Horrobin to cancer and even though Dr. Kane and Dr. Horrobin were in communication, her success was beyond the timing for sharing her results. Since then Dr. Kane and Ed Kane have lectured in the US and Europe on the IV technology she developed for clinicians under the name of the “PK Protocol”. In addition to the IV PC, BodyBio has developed an oral equivalent (BodyBio PC) that has achieved therapeutic success as well and on certain occasions is more desirable since it incorporates PE as well as PC, and as a capsule, patient acceptance and compliance are more certain than the compulsory doctor administered IV

However, there’s another chapter, the fatty acid ratio. For some time FA researchers were left with two problems 1) too much linoleic (LA n-6) in the diet (much of it hydrogenated or from overeating as in fried foods), and 2) how to fill in the all important alpha linolenic (ALA n-3) which had had been fraught with difficulty since the mid 1950-60s. The early researchers had tried flax oil, which, at ~55% ALA, amply supplied the all important need for n-3 Linolenic. They soon discovered that it was only beneficial for a short time (Joanna Budwig and Donald Rudin, even Udo Erasmus), after which the individuals developed skin and neurological problems which self-corrected if they abstained. The solution came from Yehuda, Mostofsky, Carasso and Rabinovitz from Bar Ilan University in Israel. This exceptional team under the guidance of Professor Shlomo Yehuda cracked what is probably the most important nutritional answer of our time, the dietary ratio of the Omega 6 EFAs to the Omega 3s, Linoleic to Linlolenic. Before their 1993 study “Modulation of learning, pain thresholds, and thermoregulation in the rat etc”, there had been no way to know which or how much essential oils we needed. Yehuda effectively answered that question with his SR3 1:4 ratio, one part ALA to four parts LA (20% n-3 to 80% n-6) (Yehuda et. al. 1993, 94, 95, 962, 972, 983, 992, 20002, 02, 03, 04, 052, 07, 08,etc). The value of Yehuda’s work to the health of the world is of such huge import as to warrant a nomination for a Nobel Prize. For more on this important FA question please refer to the BodyBio Bulletin on the 4-1 ratio.

“Almost fifty years after the first anti-schizophrenic drug, chlorpromazine, was produced we have made virtually no further progress in controlling schizophrenic symptoms. Drugs, on average, still improve symptoms by only 15-25 per cent, leaving 75-85 per cent of symptoms unresolved. The side-effects of Parkinsonism, tardive dyskinesia (TD) and agranulocytosis have been drastically reduced, but new side-effects of weight gain, sedation, diabetes and cardiac problems are still there and may have even worsened” (Horrobin 2001). These comments were made a decade ago prior to the current BodyBio research and the development of the PK Protocol which has witnessed significant improvements in neurological and psychotic symptoms but have only been enjoyed by those in the integrative community. The relief of symptoms, however, can be monumental for those afflicted. We invite your inquiries at BodyBio – 888 320 8338.

The information contained in this web site is for educational purposes only and is not intended or implied to be a substitute for professional medical advice. Inclusion here does not imply any endorsement or recommendation.  Always seek the advice of your physician or other qualified medical provider for all medical problems prior to starting any new regiment.

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